Pre-orgasmic sexual headache responsive to topiramate: A case report

Dear Sir,

Primary headache associated with sexual activity (HSA) is a benign form of headache that is temporally related to sexual intercourse. HSA is probably under-reported, with a lifetime prevalence estimated to be 1% in a population-based study (1). Onset usually occurs in the fourth decade of life. The International Headache Society divides it into two subtypes (2): Type 1 refers to pre-orgasmic headache, a dull ache in the head and neck that occurs during sexual activity and increases with sexual excitement. Type 2, which is more frequent (3), is orgasmic cephalalgia, sudden and severe, similar to thunderclap headache, which occurs at orgasm. Prognosis is good. However, HSA, especially type 2, needs to be distinguished from more serious conditions, such as subarachnoid haemorrhage, unruptured aneurysm, cerebral venous sinus thrombosis, arterial dissection and reversible cerebral vasoconstriction syndrome (RCVS). Therefore, for patients in whom HSA occurs for the first time, appropriate imaging studies are mandatory. We report the case of a patient with typical pre-orgasmic HSA with an optimal and prolonged response to topiramate. Topiramate could be considered as a treatment option in pre-orgasmic headache.

A 55-year-old woman was admitted to our headache clinic reporting a history of severe headache during sexual intercourse for the last 4 months. She had never had similar headaches in the past. She was a smoker (20 cigarettes daily), did not drink alcohol, and had a history of epigastric pain treated by a proton pump inhibitor. She had also a personal history of migraine without aura. Headache was localized to both the occipital and temporal regions, bilaterally, beginning as a dull pain for some minutes, slowly increasing and being most intense at orgasm. After that, it lasted about 5 minutes. Adopting a more passive role during sexual intercourse had no effect. HSA had been experienced with every orgasm and could occur at any time of the day. Sexual activity not leading to orgasm still resulted in the same type of headache. There was no nausea, vomiting, photophobia, phonophobia or osmophobia. Visual, motor or sensory disturbance were not present. The headache was unresponsive to paracetamol. Other nonsteroidal anti-inflammatory drugs (NSAIDs) were not used because of the epigastric pain. The headaches resulted in conjugal conflict as the patient avoided sexual activity because of the pain. On the first occurrence, the patient was transported by ambulance to the emergency ward, where she underwent a CT scan of the brain and a cerebrospinal fluid examination, which were both unrevealing. She was discharged from the hospital with reassurance on the benignity of her headache. When later observed, general and neurologic examinations were unremarkable, as were laboratory investigations. Magnetic resonance imaging and magnetic resonance angiography were normal, thus ruling out the possibility of intracranial lesions, such as aneurysm, arterial dissection, and RCVS. A diagnosis of primary pre-orgasmic HSA was made. Owing to her epigastric pain and regular and frequent sexual activity, the patient refused any NSAIDs and favoured a prophylactic treatment. Topiramate at an increasing dose, starting at 25 mg/day up to 100 mg/day, was prescribed. A dramatic improvement followed and HSA completely ceased. After 5 months, the patient noticed a significant weight loss (5 kg) and voluntarily decided to discontinue the treatment, with a recurrence of headache shortly after. Topiramate was then started again, at a dosage of 50 mg/day, with a clear and rapid response. The patient has been on regular follow-up once every 3 months for the past 12 months, and has reported a constant abolition of headache with topiramate prophylaxis. Her weight remained unchanged.

The present study describes one patient with a typical primary pre-orgasmic HSA, who showed an excellent response to a prophylactic treatment with topiramate 50 mg daily. The possibility of a spontaneous remission of HSA, a well-known feature of the disease, seems unlikely in our patient, given the re-occurrence of the episodes after drug withdrawal and the second, prolonged therapeutic effect. Topiramate is a relatively novel anti-epileptic drug with several putative mechanisms of action, including blockage of voltage‐sensitive sodium and calcium channels, anti-glutamatergic activity at AMPA/kainate sites, inhibition of carbonic anhydrase and augmentation of inhibitory gamma‐aminobutyric acid activity at some subtypes of the GABA-A receptors (4). Topiramate has recently been found to be effective for several neurological and psychiatric disorders, including migraine, cluster headache, painful diabetic neuropathy, essential tremor and alcohol dependence. A recent report emphasizes the efficacy of topiramate in orgasmic HSA (5). Orgasmic and pre-orgasmic HSA, however, do not share the same pathophysiological mechanisms: the former seems to be related to migraine, although alternative hypotheses (increased intracranial pressure due to a Valsalva manoeuvre during orgasm or disturbance in cerebral arterial autoregulation) have been proposed (6,7). Pre-orgasmic HSA, on the other hand, is assumed to be a subtype of tension-type headache (TTH), with muscular contraction becoming more intense as the sexual excitement increases (6,8). The beneficial effect of topiramate in pre-orgasmic HSA seems to broaden its usefulness in the treatment of pain syndromes and suggests its use as an alternative treatment for patients for whom, as in our case, the episodes are regular and frequent and NSAIDs are not suitable options. Caution is obviously needed to draw any conclusion from a study of just one patient. However, because the analgesic effect of drugs in TTH seems likely to be due to the modulation of central pain sensitivity, it is tempting to speculate that the blockage of central hyperexcitability by topiramate might have had a key role in suppressing pre-orgasmic HSA. The reported beneficial effect of topiramate for TTH (9) is consistent with this hypothesis.